A Tale of Three Doctors, a Nurse Practitioner and a Pissing Contest

Obviously, the family has lost any natural resistance to malaria over the last three years and there are two malaria prophylaxis drugs recommended for children of Kezia's age travelling to countries with malaria:

Malarone with side-effects: neutropenia, pancytopenia.

Mefloquine with side-effects: principally psychological (bad dreams etc, nothing haematological)

Kezia's consultant wrote to our GP practice in the UK requesting they prescibe Kezia with Mefloquine. Our family doctor here recommends that Kezia takes Mefloquine.

Jaime and Kezia have been taking various vaccines over the last couple of weeks. And the "Nurse Specialist in paediatric and adult vaccinations" insists that Kezia takes Malarone, that she hasn't prescribed Mefloquine in ten years, and won't, that she has much experience in malaria prophylaxis.

Has she experience in paedeatric oncology/haematology? Has she experience in paedeatric oncology/haematology in malarial zones?

My brother Pete is going to try and get through to the Doctor rather than the "Nurse Specialist" tomorrow and sort this out. Thanks bruv.

Afrox - you have a long way to go.

And Drs Crippen and Rant you will hear more from me on "Nurse Specialists".

Alphacypermethrin

I wrote here about the malaria eradication campaign in our small country led by the Taiwanese. I noted that the insecticide, alphacypermethrin, used to spray the inside of houses is claimed to be ecologically safe.

However, today I was talking to the wife of a colleague who has developed an allergy to alphacypermethrin and is being treated by our workplace doctor. So I got to looking it up on the web and found this information from the US Environmental Protection Agency:

"These modern synthetic insecticides are similar chemically to natural pyrethrins, but modified to increase stability in the natural environment. They are now widely used in agriculture, in homes and gardens, and for treatment of
ectoparasitic disease.

Pyrethroids are formulated as emulsifiable concentrates, wettable powders,granules, and concentrates for ultra low volume application. They may be combined with additional pesticides (sometimes highly toxic) in the technical product or tank-mixed with other pesticides at the time of application. AASTAR (discontinued
1992), for instance, was a combination of flucythrinate and phorate. Phorate is a highly toxic organophosphate. Nix and Elimite are permethrincreams applied to control human ectoparasites.

Toxicology

Certain pyrethroids exhibit striking neurotoxicity in laboratory animals when administered by intravenous injection, and some are toxic by the oral route. However, systemic toxicity by inhalation and dermal absorption is low. Although limited absorption may account for the low toxicity of some pyrethroids, rapid biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is probably the major factor responsible for this phenomenon. Most pyrethroid metabolites are promptly excreted, at least in part, by the kidney.

The most severe, although more uncommon, toxicity is to the central nervous system. Seizures have been reported in severe cases of pyrethroid intoxication. Of 573 cases reviewed in China, there were 51 cases with disturbed
consciousness and 34 cases with seizures. Of those, only 5 were from occupational exposure. Seizures are more common with exposure to the more toxic cyano-pyrethroids, which include fenvalerate, flucythrinate, cypermethrin,
deltapermethrin, and fluvalinate. There are no reports in the literature of seizures in humans from exposure to permethrin.

Apart from central nervous system toxicity, some pyrethroids do cause distressing paresthesias when liquid or volatilized materials contact human skin.Again, these symptoms are more common with exposure to the pyrethroids
whose structures include cyano-groups.Sensations are described as stinging, burning, itching, and tingling, progressing to numbness.The skin of the face seems to be most commonly affected, but the face, hands, forearms, and neck are sometimes involved. Sweating, exposure to sun or heat, and application of water enhance the disagreeable sensations. Sometimes the effect is noted within minutes of exposure, but a 1-2 hour delay in appearance of symptoms is more common. Sensations rarely persist more than 24 hours. Little or no inflammatory reaction is apparent where the paresthesia are reported; the effect is presumed to result from pyrethroid contact with sensory nerve endings in the skin. The paresthetic reaction is not allergic in nature, although sensitization and allergic responses have been reported as an independent phenomenon with pyrethroid exposure. Neither race, skin type, nor disposition to allergic disease affects the likelihood or severity of the reaction.

Persons treated with permethrin for lice or flea infestations sometimes experience itching and burning at the site of application, but this is chiefly an exacerbation of sensations caused by the parasites themselves, and is not typical
of the paresthetic reaction described above.

Other signs and symptoms of toxicity include abnormal facial sensation, dizziness, salivation, headache, fatigue, vomiting, diarrhea, and irritability to sound and touch. In more severe cases, pulmonary edema and muscle fasciculations can develop. Due to the inclusion of unique solvent ingredients, certain formulations of fluvalinate are corrosive to the eyes. Pyrethroids are not cholinesterase inhibitors. However, there have been some cases in which pyrethroid poisoning has been misdiagnosed as organophosphate poisoning, due to some of the similar presenting signs, and some patients have died from atropine toxicity."

I also discovered it is toxic to butterflies! Hence my suspicions expressed in the previous post have been confirmed - as I said before neither biodiversity impact assements nor epidemiological studies on adverse reactions are being undertaken. Additionally, it is being used in higher concentrations than normal in agricultural use.

Malaria Eradication

Malaria is a shitty, piss-poor, easily-prevented, easily-treated, easily-eradicable disease that kills millions throughout the world every year.

Why?

Poverty.

Let’s talk about me (as usual) and malaria first. I’ve had it too many times to count – and, hey I’m still here! The very first time was 6 months after getting back to England from a year in China and 3 months in India. I spent two weeks with flu-like symptoms in a student house during the Easter holidays and “the flu” wasn’t clearing up so I eventually ... phoned Mum and Dad and said “I’m coming home”. I got home, they took one look at me, called the GP and I was sent to hospital.

Isolation. I could be contagious. In those days (1980s) a very very simple malaria test could only be executed at the two tropical medicine hospitals in the UK so the turn-around took a few days. Whilst we waited for the results and as my paternal grandfather had died from lymphoma, they had a cancer “specialist” come and look at me. Results came back, a course of Chloroquine and off-you-go – not that they didn’t invite me back to their Friday lunchtime general-meeting of interesting cases at which I was asked all about how I had felt. … like a long case of flu …

Six months later it recurred. Remember your father, uncle, grandfather who served in S.E. Asia during the war who always had bouts of fever for years and years? Well, nowadays and in the 1980s, there is a way of getting rid of recurring malaria. Just the doctors at the local general hospital didn’t know. I went to the local GP – she was Indian – I said I’ve got malaria, I want a prescription for chloroquine. She was very sympathetic, and knew, but she said “No … if you wanted it for arthritis, fine, but for malaria I have to have a blood-test result”.

Another four days of waiting … but this time, in addition to the Chloroquine to get the malaria out of my blood, she gave me Primaquine to get it out of its safe-storage in my liver and thus prevent it from recurring.

Malaria is caused by a parasite of the genus Plasmodium. In humans there are four species that cause malaria – P. falciparum, P. malariae, P. ovale and P. vivax. P. vivax is the one that remains dormant in your liver, if not treated. P. falciparum does not but is the most dangerous and can directly kill, if not treated. All these species are transmitted into human blood through the bite of vampiric Anopheles mosquitoes.

The malaria parasites have, over the recent past (let us say 150 years) developed resistance to the drugs used to destroy them (cunning buggers). Once upon a time P. falciparum could be treated with Chloroquine – now it is all but useless.

In our tiny African country, malaria has been a major killer ever since it was colonised (it was uninhabited at colonisation). The principle parasite is P. falciparum, although very small percentages of the other species do occur. As our country consists of two small islands at some distance from the continent, we are an ideal testing-bed for eradicating the disease – this has been achieved on other islands, for example, in the Pacific, the most notable and most relevant to this post being Taiwan which was certified as malaria-free in 1965. This is equally borne out by two outbreaks of the sleeping-sickness vector, the tse-tse fly, in the last century on the smaller of our two islands and which was eradicated twice.

Back in 1982 a WHO-sponsored initiative attempted to eradicate the malaria vector, Anopheles mosquitoes, using the notorious insecticide DDT. Although the incidence of malaria decreased, it also resulted in the death of much poultry and livestock. The campaign was “imposed”, was not integrated, was resented, was not sustained and malaria made a comeback with a vengeance.

In 2002-2003 another attempt began receiving a range of inputs from a range of donors. US and Portuguese research, education and promotion of impregnated mosquito nets by the Seventh Day Adventist development agency ADRA etc etc.

But the biggest input has been from the Taiwanese. They have some experience in its eradication.

The Taiwanese part of the programme has two main components:

• prevention through the spraying of house interiors.

• treatment with the latest anti-malarial medications.
  

The insecticide used is Alphacypermethrin. This does not require a general fumigation, as DDT, but is sprayed on the interior walls of houses. The mode of action is surprisingly simple - the mosquito bites an infected sleeping person, has a good meal and then goes off to have a fatal siesta on the nearest impregnated wall.

Supposedly, the effect of one application will last 400 days – but I am sure this will vary with the absorption capacity of the surface being sprayed. Untreated wood, varnished or painted wood or cement block, matt or gloss.

The Taiwanese claim that Alphacypermethrin is ecologically safe. However, there is no biodiversity impact evaluation as part of the study. I have certainly noticed a decline in butterflies in recent years – this could just as well be due to other factors (e.g. climate change) but monitoring could be worthwhile both for human health and biodiversity.

The second component of the Taiwanese programme is treatment. The traditional treatment, chloroquine, has been largely ineffective for several years as Plasmodium falciparum has become resistant to it. Various other drugs have been used here – Quinine, Fansidar, Mefloquine, Halfan etc – but there were no guidelines and each doctor would prescribe what s/he felt fit.

Now we are using in the first line a combination treatment of Amodiaquine and Artesunate. Clearly, the former is part of the quinine family (of which I haven’t studied the modes of action as I have with the chemotherapy drugs Kezia is taking). The latter has a fascinating history!

The mainland Chinese started studying the anti-malarial effects of the traditional anti-malarial medicine derived from the plant Artemisa anna back in the 1960s. For various reasons, including the upheavals of the Cultural Revolution, the positive results were not published internationally. When they were, in the 1990s, they were pretty much “poohed-poohed” by the developed world except … the pharmaceuticals who pricked up their ears and went for it big time! The plant’s active ingredient was Artemisin and soon the synthetic Artesunate was developed.

Artesunate is fast-acting but has a very short half-life (i.e. very quickly disappears from the blood). Amodiaquine has longer half-life. The tablets are marketed in packs of a pair a day. If there is still some residual malaria, then a second line of attack is used – the trade name Coartem, a combination of Artesunate and Lumefantrine (in turn developed from halofantrine, the basis of Halfan, which at the time of its recent development was revolutionary in its approach to killing malaria parasites).

Prophylaxis, if you are pregnant or a tourist, is more controversial and I won’t deal with here.

Anyway, the initial Taiwanese trial on our smaller island saw the hospital’s 21 beds in two months go from 100% occupation to 0% occupation. Two years later the hospital internment rates from malaria had maintained, indicating the mosquito had not developed resistance to the insecticide and the malaria parasite had not developed resistance to the treatment medications.

The programme has now been introduced to the larger island.

Malaria

John Crippen at NHS Blog Doctor has written about malaria prophylaxis for tourists not being covered by the NHS. I totally agree with you John.

Living in a high malaria zone and having had malaria too many times to remember (first time amost 25 years ago) I think I am somewhat qualified to comment.

Firstly, if you can afford to take a holiday in a malaria zone, then you can afford malaria medication. Secondly, if you don't, you put your once-in-a-lifetime holiday at risk. Five days into your fortnight's holiday you come down with it and, even if it's only a mild attack, your holiday is ruined.

MK Student in the post's comments complains that he is going to do community work in a hospital in Ghana and still has to pay for the medication. I did three years here as a VSO volunteer – VSO rightly picked up the tab for vaccinations and malaria prophylaxis. Any organisation sending people to malaria zones should do this – if they don't, they are irresponsible.

That said I don't take malaria prophylaxis any more – I've been here too long, I cannot take it my whole life. But most people here generally know the danger signs. If you have a fever, unusual aches, anything, you don't think the flu, you think malaria and get tested for it. You have to know how to bring your temperature down with paracetamol and cold showers as well - I've brought myself back from almost unconsciousness by lowering my temperature.

I also ensure I carry malaria treatment medication with me when I travel abroad - my first experience of malaria was six months after geting back to the UK in the early '80s - I sat at home for three weeks getting weaker and weaker trying to shake off the 'flu before heading back to my parents. Immediate hospitalisation and isolation. They even suspected leukaemia at one point! The second time I knew what it was but the doctor coudn't give me a prescription until the test results came back - several days. I believe awareness, diagnosis and treatment have improved alot since the '80s but if I have the medication on hand and the malaria strikes on Sunday night, I am prepared.

Yes, it is the biggest cause of death here, generally through people not treating it properly but public health campaigns, impregnated mosquito nets, changes to treatment regimes and most recently a country-wide insecticide spraying campaign are beginning to work now.